Macromolecular NO‐Donor Micelles for Targeted and Augmented Chemotherapy against Prostate Cancer. Issue 6 (4th December 2022)

• Record Type: Journal Article
• Authors: Chen, Jiaxin; Zhao, Bingbing; Zou, Junhui; Yang, Jiachen; Yang, Lifen; Zhang, Junmei; Chen, Wei; Huang, Dechun; Zhong, Yinan
• Is Part Of: Advanced healthcare materials. Volume 12:Issue 6(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-04
• Subjects: DNA lesions -- mitoxantrone -- nitric oxide -- oxidative stress -- targeted prostate cancer therapy; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202202266
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: Mitoxantrone (MTO) is clinically utilized for treating hormone‐refractory prostate cancer (PCa), however, the therapeutic outcome is far from optimal due to the lack of proper drug carrier as well as the inherent MTO detoxification mechanisms of DNA lesion repair and anti‐oxidation. Herein, a bombesin‐installed nanoplatform combining the chemotherapeutic MTO and the chemotherapeutic sensitizer of nitric oxide (NO) is developed based on MTO‐loaded macromolecular NO‐donor‐containing polymeric micelles (BN‐NMMTO ) for targeted NO‐sensitized chemotherapy against PCa. BN‐NMMTO actively target and accumulates in PCa sites and are internalized into the tumor cells. The macromolecular NO‐donor of BN‐NMMTO undergoes a reductive reaction to unleash NO upon intracellular glutathione (GSH), accompanying by micelle swelling and MTO release. The targeted intracellular MTO release induces DNA lesion and reactive oxygen species (ROS) generation in tumor cells without damage to the normal cells, and MTO's cytotoxicity is further augmented by NO release via the inhibition of both DNA repair and anti‐oxidation pathways as compared with traditional MTO therapies. Abstract : A bombesin‐installed chemotherapeutic MTO‐loaded macromolecular NO‐donor‐containing polymeric micelle (BN‐NMMTO ) mediates targeted NO‐augmented chemotherapy against PCa via inhibition of both DNA repair and anti‐oxidation pathways which are encountered in the traditional MTO therapies, thus bringing about prominent tumor shrinkage in a PC‐3 tumor bearing mice model and providing a potential clinical alternative for PCa therapy.